The invention relates to the use of platelet-derived growth factor (PDGF) to stimulate ophthalmic wound healing, particularly wounds to the cornea.
Corneal wounds frequently arise from trauma to the eye, such as may occur in automobile accidents, industrial accidents, and wounds caused by weapons. Wounds to the eye also occur as the unavoidable consequence of surgery, such as cataract surgery, penetrating keratoplasty, glaucoma filtering surgery, retinal surgery such as retinal reattachment, and refractive surgery such as laser corneal ablation or radial keratotomy. Non-healing corneal ulcers may also arise from pathological non-traumatic causes, such as diabetes.
The healing of these wounds can frequently be slow and difficult, complicating recovery from trauma or the post-operative course of surgery. There is, therefore, a need for a readily applicable method of accelerating ophthalmic wound healing, particularly of corneal wounds.
Additionally, the quality of healing of corneal wounds is frequently poor, leading to scarring and other vision-impairing consequences. Therefore, there also is a need for a method that can improve the quality of healing of corneal wounds.
Recently, much attention has been paid to the use of growth factors to accelerate wound healing, particularly of skin. Growth factors are agents which cause cells to migrate, differentiate, transform, or mature and divide. These factors are polypeptides which can usually be isolated from many different normal and malignant mammalian cell types. Some growth factors can be produced by genetically-engineered microorganisms such as bacteria (Escherichia coli) and yeasts. See, for example, Chapters 10 and 11 of Molecular and Cellular Biology of Wound Repair (1986), incorporated herein by reference. Among these growth factors are included epidermal growth factor (EGF), transforming growth factors alpha and beta (TGF.alpha., TGF.beta..sub.1, and TGF.beta..sub.2), fibroblast growth factor (FGF), insulin-like growth factor (IGF), nerve growth factor (NGF), and platelet-derived growth factor (PDGF). These are described in U.S. Pat. No. 4,939,135 to Robertson et al., incorporated herein by this reference.
The use of PDGF to accelerate wound healing in skin and connective tissue has been studied (Antoniades et al., Proc. Natl. Acad. Sci. USA 88:565-569 (1991); Cromack et al., J. Trauma 30:S129-133 (1990); Ross et al., Philos. Trans. R. Soc. Lond. (Biol.) 327:155-169 (1990)). However, conditions in the cornea are substantially different than those in skin and connective tissue. For example, the corneal epithelium is continually washed with tear fluid which contains a significant quantity of EGF. It is believed that the presence of one growth factor may compete for or interfere with the response to other growth factors (Adelman-Grill et al., Eur. J. Cell. Biol. 51:322-326 (1990)). Thus, there is a need for a growth factor that will work in corneal tissue as opposed to skin or connective tissue, and that can work to promote corneal wound healing even in the presence of other growth factors.
Additionally, re-innervation of the cornea is highly desirable but frequently is delayed during healing. Failure of re-innervation can lead to loss of function, such as the failure of maintenance of the corneal epithelium. It is therefore desirable that a treatment that accelerates corneal wound healing also accelerates re-innervation.